Is MPEG1 p.Ser224Phe (c.671C>T) pathogenic?

MPEG1 p.Ser224Phe (c.671C>T) is classified Likely benign in MPEG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). AlphaMissense: likely benign (0.1866); Low-frequency (popmax 1.15%, mid).

How common is MPEG1 p.Ser224Phe (c.671C>T) in the general population?

MPEG1 p.Ser224Phe (c.671C>T) is low-frequency (popmax 1.15%, mid) (gnomAD).

What do computational predictors say about MPEG1 p.Ser224Phe (c.671C>T)?

AlphaMissense predicts likely benign (score 0.1866) — an in-silico prediction, not a clinical call.

MPEG1 p.Ser224Phe

c.671C>T · rs199564440 · VCV2641810

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1866 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1866	likely benign
REVEL	0.581	indeterminate
SaProt	LLR -11.89	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 2,147 bp · p 0.89 · regional, not allelic
Overall
CADD	24.3	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 1.15% Middle Eastern · 70/6,062 alleles

Filtering AF 0.937% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.858%

Overall 0.0737% 1,189/1,614,032 alleles · low-frequency exomes 1,119/1,461,714 · genomes 70/152,318 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.15%	87
South Asian	0.733%	136
Remaining individualsnot grpmax-eligible	0.118%	845
Admixed American	0.055%	1,819
European (non-Finnish)	0.0284%	3,522
African / African-American	0.00933%	10,723
East Asian	0.00446%	22,442

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: MPEG1
Protein: p.Ser224Phe
Coding: c.671C>T
MANE Select: NM_001039396
dbSNP: rs199564440
Type: single nucleotide variant
Location: chr11:59212195 (GRCh38)
Gene constraint: LOEUF 1.941 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 83.22 · 5 PDB
Residue 224: an α-helix; the macpf domain

Full MPEG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MPEG1 p.Ala525Val Uncertain significance ★★ ⚠ same type
MPEG1 p.Gln259Glu Uncertain significance ★★ ⚠ same type
MPEG1 p.Gln713Arg Uncertain significance ★★ ⚠ same type
MPEG1 p.His420Tyr Uncertain significance ★★ ⚠ same type
MPEG1 p.Ala467= Benign ★★ same type
MPEG1 p.Thr73Ala Likely benign ★★ same type
MPEG1 p.Ala238Thr Uncertain significance ★ ⚠ same type
MPEG1 p.Ala238Val Uncertain significance ★ ⚠ same type

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/mpeg1-p-ser224phe (accessed [today's date]).

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