Is MOCOS p.Val385Phe (c.1153G>T) pathogenic?

MOCOS p.Val385Phe (c.1153G>T) is classified Uncertain significance in MOCOS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-03). AlphaMissense: likely benign (0.0915); Ultra-rare (popmax 0.0227%, afr).

How common is MOCOS p.Val385Phe (c.1153G>T) in the general population?

MOCOS p.Val385Phe (c.1153G>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about MOCOS p.Val385Phe (c.1153G>T)?

AlphaMissense predicts likely benign (score 0.0915) — an in-silico prediction, not a clinical call.

MOCOS p.Val385Phe

c.1153G>T · VCV3873928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0915 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0915	likely benign
REVEL	0.291	indeterminate
SaProt	LLR -7.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 81 kb · p 0.84 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/74,848 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00136% 22/1,613,762 alleles · ultra-rare exomes 9/1,461,762 · genomes 13/152,000 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,403
Admixed American	0.00834%	11,998

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: MOCOS
Protein: p.Val385Phe
Coding: c.1153G>T
MANE Select: NM_017947
Type: single nucleotide variant
Location: chr18:36205211 (GRCh38)
Gene constraint: LOEUF 1.19 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.88

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

Similar variants

MOCOS c.1218+1G>C Likely pathogenic ★★ same type
MOCOS c.2164+2T>C Likely pathogenic ★★ same type
MOCOS c.232+1G>A Likely pathogenic ★★ same type
MOCOS p.Arg419Ter Pathogenic ★★ same type
MOCOS p.Arg776Cys Pathogenic/Likely pathogenic ★★ same type
MOCOS p.Gln516Ter Likely pathogenic ★★ same type
MOCOS p.Glu42Ter Likely pathogenic ★★ same type
MOCOS p.Glu763Ter Likely pathogenic ★★ 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/mocos-p-val385phe (accessed [today's date]).

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