Is DAAM2 p.Ser279Phe (c.836C>T) pathogenic?

DAAM2 p.Ser279Phe (c.836C>T) is classified Likely benign in DAAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-27). AlphaMissense: likely pathogenic (0.981); Rare (popmax 0.43%, sas); Associated with DAAM2-related disorder.

What condition is associated with DAAM2 p.Ser279Phe (c.836C>T)?

DAAM2 p.Ser279Phe (c.836C>T) is associated with DAAM2-related disorder (ClinVar).

How common is DAAM2 p.Ser279Phe (c.836C>T) in the general population?

DAAM2 p.Ser279Phe (c.836C>T) is rare (popmax 0.43%, sas) (gnomAD).

What do computational predictors say about DAAM2 p.Ser279Phe (c.836C>T)?

AlphaMissense predicts likely pathogenic (score 0.981) — an in-silico prediction, not a clinical call.

DAAM2 p.Ser279Phe

c.836C>T · rs551076398 · VCV3042784

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.981 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.43%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DAAM2-related disorder

Computational evidence

Protein change
AlphaMissense	0.981	likely pathogenic
REVEL	0.93	moderately pathogenic-leaning
SaProt	LLR -11.88	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 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 11 kb · p 5e-07 · regional, not allelic
Overall
CADD	32.0	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 0.43% South Asian · 371/86,308 alleles

Filtering AF 0.394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.38%

Overall 0.0241% 383/1,586,610 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.43%	233
Middle Eastern	0.0497%	2,012
Remaining individualsnot grpmax-eligible	0.0114%	8,793
East Asian	0.0023%	43,470
European (non-Finnish)	8.57e-05%	1,166,416

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: DAAM2
Protein: p.Ser279Phe
Coding: c.836C>T
MANE Select: NM_001201427
dbSNP: rs551076398
Type: single nucleotide variant
Location: chr6:39868896 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 279: the gbd/fh3 domain

Full DAAM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DAAM2-related disorder

Similar variants

DAAM2 p.Ala829Thr Uncertain significance ⚠ same condition
DAAM2 p.Glu997Lys Uncertain significance same condition
DAAM2 p.Gly527Val Uncertain significance ⚠ same condition
DAAM2 c.1845+7A>G Likely benign same condition
DAAM2 c.2342-10C>T Likely benign same condition
DAAM2 c.2983-4G>A Likely benign same condition
DAAM2 c.2983-8G>C Likely benign same condition
DAAM2 p.Ala1054Thr Likely benign 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/daam2-p-ser279phe (accessed [today's date]).

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