Is MFSD8 p.Phe379Ser (c.1136T>C) pathogenic?

MFSD8 p.Phe379Ser (c.1136T>C) is classified Conflicting classifications of pathogenicity in MFSD8 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-04-23). AlphaMissense: likely benign (0.0834); Ultra-rare (popmax 0.0516%, amr); Associated with Inborn genetic diseases.

What condition is associated with MFSD8 p.Phe379Ser (c.1136T>C)?

MFSD8 p.Phe379Ser (c.1136T>C) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis 7, macular dystrophy with central cone involvement (ClinVar).

How common is MFSD8 p.Phe379Ser (c.1136T>C) in the general population?

MFSD8 p.Phe379Ser (c.1136T>C) is ultra-rare (popmax 0.0516%, amr) (gnomAD).

What do computational predictors say about MFSD8 p.Phe379Ser (c.1136T>C)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

MFSD8 p.Phe379Ser

c.1136T>C · rs191172038 · VCV206161

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0516%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -4.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 44 kb · p 0.0019 · regional, not allelic
Overall
CADD	19.05	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0516% Admixed American · 31/60,020 alleles

Filtering AF 0.0374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.0294% 474/1,614,166 alleles · ultra-rare exomes 427/1,461,864 · genomes 47/152,302 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0516%	1,936
European (non-Finnish)	0.0348%	2,871
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,290
Remaining individualsnot grpmax-eligible	0.0224%	4,464
South Asian	0.00329%	30,359
Finnishnot grpmax-eligible	0.00312%	32,015
African / African-American	0.00266%	37,526

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MFSD8
Protein: p.Phe379Ser
Coding: c.1136T>C
MANE Select: NM_001371596
dbSNP: rs191172038
Type: single nucleotide variant
Location: chr4:127921738 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.20

Full MFSD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuronal ceroid lipofuscinosis 7 macular dystrophy with central cone involvement late infantile neuronal ceroid lipofuscinosis

Similar variants

MFSD8 p.Phe379Ile Uncertain significance ★★ ⚠ same residue
MFSD8 c.1102+1G>A Likely pathogenic ★★ same condition
MFSD8 c.1102+2T>C Pathogenic/Likely pathogenic ★★ same condition
MFSD8 c.1350+2T>C Pathogenic/Likely pathogenic ★★ same condition
MFSD8 c.154+1G>A Likely pathogenic ★★ same condition
MFSD8 c.198+2T>C Pathogenic/Likely pathogenic ★★ same condition
MFSD8 c.439+2T>A Likely pathogenic ★★ same condition
MFSD8 c.440-2A>T Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mfsd8-p-phe379ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown