Is MAP4 p.Phe103Ser (c.308T>C) pathogenic?

MAP4 p.Phe103Ser (c.308T>C) is classified Uncertain significance in MAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: ambiguous (0.4999); Very rare (popmax 0.00297%, nfe).

How common is MAP4 p.Phe103Ser (c.308T>C) in the general population?

MAP4 p.Phe103Ser (c.308T>C) is very rare (popmax 0.00297%, nfe) (gnomAD).

What do computational predictors say about MAP4 p.Phe103Ser (c.308T>C)?

AlphaMissense predicts ambiguous (score 0.4999) — an in-silico prediction, not a clinical call.

MAP4 p.Phe103Ser

c.308T>C · rs745834831 · VCV2475461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4999	ambiguous
REVEL	0.227	benign-leaning
SaProt	LLR -4.52	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 0.45, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 123 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	22.0	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 0.00297% European (non-Finnish) · 35/1,180,004 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00223% 36/1,613,992 alleles · very rare exomes 34/1,461,804 · genomes 2/152,188 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00297%	33,714
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: MAP4
Protein: p.Phe103Ser
Coding: c.308T>C
MANE Select: NM_001385682
dbSNP: rs745834831
Type: single nucleotide variant
Location: chr3:47928335 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03

Full MAP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP4 c.292+9T>G Benign ★★ same type
MAP4 p.Gln1950= Benign ★★ same type
MAP4 p.Leu516= Likely benign ★★ same type
MAP4 p.Val37= Benign ★★ same type
MAP4 p.Ala150Ser Uncertain significance ★ ⚠ same type
MAP4 p.Ala1922Val Uncertain significance ★ ⚠ same type
MAP4 p.Ala1926Pro Uncertain significance ★ ⚠ same type
MAP4 p.Ala1941Thr 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/map4-p-phe103ser (accessed [today's date]).

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