Is DNAAF3 p.Arg162Ser (c.484C>A) pathogenic?

DNAAF3 p.Arg162Ser (c.484C>A) is classified Uncertain significance in DNAAF3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-17). AlphaMissense: likely pathogenic (0.9477); Very rare (popmax 0.00511%, nfe); Associated with cardiomyopathy, familial restrictive, 1.

What condition is associated with DNAAF3 p.Arg162Ser (c.484C>A)?

DNAAF3 p.Arg162Ser (c.484C>A) is associated with cardiomyopathy, familial restrictive, 1, dilated cardiomyopathy 2A, hypertrophic cardiomyopathy 7 (ClinVar).

How common is DNAAF3 p.Arg162Ser (c.484C>A) in the general population?

DNAAF3 p.Arg162Ser (c.484C>A) is very rare (popmax 0.00511%, nfe) (gnomAD).

What do computational predictors say about DNAAF3 p.Arg162Ser (c.484C>A)?

AlphaMissense predicts likely pathogenic (score 0.9477) — an in-silico prediction, not a clinical call.

DNAAF3 p.Arg162Ser

c.484C>A · rs760391305 · VCV894094

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9477 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00511%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cardiomyopathy, familial restrictive, 1

Computational evidence

Protein change
AlphaMissense	0.9477	likely pathogenic · top 6% in DNAAF3
REVEL	0.272	benign-leaning
SaProt	LLR -10.29	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 8.2	GERP 0.38, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 7,348 bp · p 0.5 · regional, not allelic
Overall
CADD	26.2	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 0.00511% European (non-Finnish) · 56/1,096,570 alleles

Filtering AF 0.00403% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.00411% 59/1,436,048 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00511%	19,582
Remaining individualsnot grpmax-eligible	0.00362%	27,621
Admixed American	0.0027%	37,068

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: DNAAF3
Protein: p.Arg162Ser
Coding: c.484C>A
MANE Select: NM_001256715
dbSNP: rs760391305
Type: single nucleotide variant
Location: chr19:55161822 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.06

Full DNAAF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardiomyopathy, familial restrictive, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 2A hypertrophic cardiomyopathy 7 primary ciliary dyskinesia

Similar variants

DNAAF3 p.Arg162Leu Uncertain significance ★ ⚠ same residue
DNAAF3 c.789+1G>C Likely pathogenic ★★ same condition
DNAAF3 p.Asn252Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
DNAAF3 p.Gln301Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF3 c.789+5G>C Uncertain significance ★★ same condition
DNAAF3 c.-37G>A Uncertain significance ★★ same condition
DNAAF3 p.Ala128Thr Uncertain significance ★★ ⚠ same condition
DNAAF3 p.Ala256Gly Uncertain significance ★★ ⚠ same condition

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/dnaaf3-p-arg162ser (accessed [today's date]).

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