Is SLC19A1 p.Asn277Ser (c.830A>G) pathogenic?

SLC19A1 p.Asn277Ser (c.830A>G) is classified Uncertain significance in SLC19A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: likely benign (0.0539); Very rare (popmax 0.00144%, nfe).

How common is SLC19A1 p.Asn277Ser (c.830A>G) in the general population?

SLC19A1 p.Asn277Ser (c.830A>G) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about SLC19A1 p.Asn277Ser (c.830A>G)?

AlphaMissense predicts likely benign (score 0.0539) — an in-silico prediction, not a clinical call.

SLC19A1 p.Asn277Ser

c.830A>G · rs1486330835 · VCV2299908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0539 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0539	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -2.15	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.69	GERP -3.1, phastCons 0.039
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.89 · regional, not allelic
Overall
CADD	19.24	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 0.00144% European (non-Finnish) · 17/1,179,696 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00105% 17/1,612,370 alleles · very rare exomes 17/1,460,528 · genomes 0/151,842 · joint denominator

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: SLC19A1
Protein: p.Asn277Ser
Coding: c.830A>G
MANE Select: NM_194255
dbSNP: rs1486330835
Type: single nucleotide variant
Location: chr21:45531508 (GRCh38)
Gene constraint: LOEUF 1.585 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.30 · 19 PDB
Residue 277: an α-helix

Full SLC19A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL18A1 p.Arg1081Ter Pathogenic/Likely pathogenic ★★ same type
COL18A1 p.Arg915Ter Pathogenic/Likely pathogenic ★★ same type
RFC1 p.Arg383Ter Pathogenic/Likely pathogenic ★★ same type
COL18A1 c.*30G>A Uncertain significance ★★ same type
COL18A1 p.Ala1089Thr Uncertain significance ★★ ⚠ same type
COL18A1 p.Ala1254Val Uncertain significance ★★ ⚠ same type
COL18A1 p.Arg1081Gln Uncertain significance ★★ ⚠ same type
COL18A1 p.Arg1183His 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/slc19a1-p-asn277ser (accessed [today's date]).

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