Is DRC5 p.Phe91Ser (c.272T>C) pathogenic?

DRC5 p.Phe91Ser (c.272T>C) is classified Uncertain significance in DRC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: likely pathogenic (0.8312); Very rare (popmax 0.0029%, nfe).

How common is DRC5 p.Phe91Ser (c.272T>C) in the general population?

DRC5 p.Phe91Ser (c.272T>C) is very rare (popmax 0.0029%, nfe) (gnomAD).

What do computational predictors say about DRC5 p.Phe91Ser (c.272T>C)?

AlphaMissense predicts likely pathogenic (score 0.8312) — an in-silico prediction, not a clinical call.

DRC5 p.Phe91Ser

c.272T>C · rs372275761 · VCV2387417

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8312 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0029%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8312	likely pathogenic · top 6% in DRC5
REVEL	0.767	pathogenic-leaning
SaProt	LLR -12.63	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 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,641 bp · p 0.39 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0029% European (non-Finnish) · 34/1,174,094 alleles

Filtering AF 0.00208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00184%

Overall 0.0023% 37/1,606,426 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0029%	34,532
Admixed American	0.00167%	59,832
Remaining individualsnot grpmax-eligible	0.00161%	62,156
Finnishnot grpmax-eligible	0.00157%	63,868

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: DRC5
Protein: p.Phe91Ser
Coding: c.272T>C
MANE Select: NM_182539
dbSNP: rs372275761
Type: single nucleotide variant
Location: chr6:44287554 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 1 PDB

Full DRC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC5 p.Ala351Asp Uncertain significance ★ ⚠ same type
DRC5 p.Ala381Thr Uncertain significance ★ ⚠ same type
DRC5 p.Ala385Gly Uncertain significance ★ ⚠ same type
DRC5 p.Arg133His Uncertain significance ★ ⚠ same type
DRC5 p.Arg133Pro Uncertain significance ★ ⚠ same type
DRC5 p.Arg158Gln Uncertain significance ★ ⚠ same type
DRC5 p.Arg185Gly Uncertain significance ★ ⚠ same type
DRC5 p.Arg185Trp 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/drc5-p-phe91ser (accessed [today's date]).

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