Is DMAP1 p.Thr277Ser (c.830C>G) pathogenic?

DMAP1 p.Thr277Ser (c.830C>G) is classified Uncertain significance in DMAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: likely benign (0.0756); Ultra-rare (popmax 0.011%, sas).

How common is DMAP1 p.Thr277Ser (c.830C>G) in the general population?

DMAP1 p.Thr277Ser (c.830C>G) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about DMAP1 p.Thr277Ser (c.830C>G)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

DMAP1 p.Thr277Ser

c.830C>G · VCV3502506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -5.89	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 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 1,518 bp · p 2.6e-10 · regional, not allelic
Overall
CADD	19.87	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.011% South Asian · 10/91,084 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00421% 68/1,614,092 alleles · ultra-rare exomes 62/1,461,870 · genomes 6/152,222 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0312%	3,201
South Asiangrpmax	0.011%	9,108
Remaining individualsnot grpmax-eligible	0.0096%	10,414
European (non-Finnish)	0.00263%	38,066
Admixed American	0.00167%	60,012

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DMAP1
Protein: p.Thr277Ser
Coding: c.830C>G
MANE Select: NM_019100
Type: single nucleotide variant
Location: chr1:44219165 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.46 · 18 PDB
Residue 277: the 'disordered' region

Full DMAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMAP1 p.Arg224Ter Uncertain significance ★★ same type
DMAP1 p.Arg283His Uncertain significance ★★ ⚠ same type
DMAP1 p.Tyr196Ser Uncertain significance ★★ ⚠ same type
DMAP1 p.Arg226Trp Likely pathogenic ★ same type
DMAP1 c.1344+3A>G Uncertain significance ★ same type
DMAP1 c.394-1G>C Uncertain significance ★ same type
DMAP1 p.Ala207Thr Uncertain significance ★ ⚠ same type
DMAP1 p.Ala2Thr 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/dmap1-p-thr277ser (accessed [today's date]).

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