Is MAP4 p.Ser2141Phe (c.6422C>T) pathogenic?

MAP4 p.Ser2141Phe (c.6422C>T) is classified Likely benign in MAP4 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-01). AlphaMissense: likely pathogenic (0.8083); Rare (popmax 0.531%, nfe).

How common is MAP4 p.Ser2141Phe (c.6422C>T) in the general population?

MAP4 p.Ser2141Phe (c.6422C>T) is rare (popmax 0.531%, nfe) (gnomAD).

What do computational predictors say about MAP4 p.Ser2141Phe (c.6422C>T)?

AlphaMissense predicts likely pathogenic (score 0.8083) — an in-silico prediction, not a clinical call.

MAP4 p.Ser2141Phe

c.6422C>T · rs150907099 · VCV3039009

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8083 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.531%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8083	likely pathogenic · top 9% in MAP4
REVEL	0.672	pathogenic-leaning
SaProt	LLR -10.59	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 23 kb · p 0.28 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S996F vs ClinVar S2141F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.531% European (non-Finnish) · 6,257/1,178,110 alleles

Filtering AF 0.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.516%

Overall 0.437% 7,050/1,611,796 alleles · rare exomes 6,527/1,459,578 · genomes 523/152,218 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.43%	70
European (non-Finnish)grpmax	0.531%	188
Remaining individualsnot grpmax-eligible	0.452%	221
Admixed American	0.367%	272
Middle Eastern	0.298%	336
South Asian	0.164%	610
African / African-American	0.0854%	1,171
Ashkenazi Jewishnot grpmax-eligible	0.071%	1,409
Finnishnot grpmax-eligible	0.0375%	2,667
East Asian	0.00446%	22,442

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser2141Phe
Coding: c.6422C>T
MANE Select: NM_001385682
dbSNP: rs150907099
Type: single nucleotide variant
Location: chr3:47867325 (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-ser2141phe (accessed [today's date]).

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