Is DAAM2 p.Ile856Thr (c.2567T>C) pathogenic?

DAAM2 p.Ile856Thr (c.2567T>C) is classified Likely benign in DAAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-26). AlphaMissense: likely benign (0.2216); Rare (popmax 0.703%, nfe); Associated with DAAM2-related disorder.

What condition is associated with DAAM2 p.Ile856Thr (c.2567T>C)?

DAAM2 p.Ile856Thr (c.2567T>C) is associated with DAAM2-related disorder (ClinVar).

How common is DAAM2 p.Ile856Thr (c.2567T>C) in the general population?

DAAM2 p.Ile856Thr (c.2567T>C) is rare (popmax 0.703%, nfe) (gnomAD).

What do computational predictors say about DAAM2 p.Ile856Thr (c.2567T>C)?

AlphaMissense predicts likely benign (score 0.2216) — an in-silico prediction, not a clinical call.

DAAM2 p.Ile856Thr

c.2567T>C · rs61748650 · VCV3038271

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2216 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.703%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DAAM2-related disorder

Computational evidence

Protein change
AlphaMissense	0.2216	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.46 · regional, not allelic
Overall
CADD	22.1	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 0.703% European (non-Finnish) · 8,292/1,179,672 alleles

Filtering AF 0.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.685%

Overall 0.578% 9,322/1,613,740 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.703%	142
Remaining individualsnot grpmax-eligible	0.552%	181
Finnishnot grpmax-eligible	0.422%	237
Admixed American	0.253%	395
South Asian	0.201%	498
African / African-American	0.0973%	1,028
Middle Eastern	0.066%	1,516
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
East Asian	0.00223%	44,868

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: DAAM2
Protein: p.Ile856Thr
Coding: c.2567T>C
MANE Select: NM_001201427
dbSNP: rs61748650
Type: single nucleotide variant
Location: chr6:39897231 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 856: a UniProt-annotated variant site (in nphs24; affects the regulation of filopodia formation); the fh2 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-ile856thr (accessed [today's date]).

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