Is DNAAF4 p.Val91Phe (c.271G>T) pathogenic?

DNAAF4 p.Val91Phe (c.271G>T) is classified Uncertain significance in DNAAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-20). AlphaMissense: likely benign (0.0848); Very rare (popmax 0.00179%, nfe).

How common is DNAAF4 p.Val91Phe (c.271G>T) in the general population?

DNAAF4 p.Val91Phe (c.271G>T) is very rare (popmax 0.00179%, nfe) (gnomAD).

What do computational predictors say about DNAAF4 p.Val91Phe (c.271G>T)?

AlphaMissense predicts likely benign (score 0.0848) — an in-silico prediction, not a clinical call.

DNAAF4 p.Val91Phe

c.271G>T · rs17819126 · VCV1013641

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0848 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00179%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0848	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -10.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.29	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.78	GERP 1.2, phastCons 0.21
Regional constraint	o/e 1.18	unconstrained · MANE · 68 kb · p 7.4e-05 · regional, not allelic
Overall
CADD	21.5	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 0.00179% European (non-Finnish) · 21/1,175,550 alleles

Filtering AF 0.00115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000974%

Overall 0.00137% 22/1,600,004 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00179%	55,979
Remaining individualsnot grpmax-eligible	0.00162%	61,854

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: DNAAF4
Protein: p.Val91Phe
Coding: c.271G>T
MANE Select: NM_130810
dbSNP: rs17819126
Type: single nucleotide variant
Location: chr15:55497712 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.00
Residue 91: a UniProt-annotated variant site (in); the 'mediates interaction with esr1 and stub1' region

Full DNAAF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAAF4 p.Val91Ile Benign ★★ ⚠ same residue
DNAAF4 c.1047+1G>A Pathogenic/Likely pathogenic ★★ same type
DNAAF4 c.1153+1G>A Pathogenic ★★ same type
DNAAF4 c.405+1G>A Likely pathogenic ★★ same type
DNAAF4 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same type
DNAAF4 p.Arg270Ter Pathogenic/Likely pathogenic ★★ same type
DNAAF4 p.Arg330Trp Pathogenic/Likely pathogenic ★★ same type
DNAAF4 p.Arg371Ter Pathogenic/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/dnaaf4-p-val91phe (accessed [today's date]).

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